Abstract
Density functional theory (DFT) is a powerful computational tool to enable structural interpretations of NMR spin–spin coupling constants ( J-couplings) in saccharides, including the abundant 1H–1H ( J HH), 13C–1H ( J CH), and 13C–13C ( J CC) values that exist for coupling pathways comprised of 1–4 bonds. The multiple hydroxyl groups in saccharides, with their attendant lone-pair orbitals, exert significant effects on J-couplings that can be difficult to decipher and quantify without input from theory. Oxygen substituent effects are configurational and conformational in origin (e.g., axial/equatorial orientation of an OH group in an aldopyranosyl ring; C–O bond conformation involving an exocyclic OH group). DFT studies shed light on these effects, and if conducted properly, yield quantitative relationships between a specific J-coupling and one or more conformational elements in the target molecule. These relationships assist studies of saccharide structure and conformation in solution, which are often challenged by the presence of conformational averaging. Redundant J-couplings, defined as an ensemble of J-couplings sensitive to the same conformational element, are particularly helpful when the element is flexible in solution (i.e., samples multiple conformational states on the NMR time scale), provided that algorithms are available to convert redundant J-values into meaningful conformational models. If the latter conversion is achievable, the data can serve as a means of testing, validating, and refining theoretical methods like molecular dynamics (MD) simulations, which are currently relied upon heavily to assign conformational models of saccharides in solution despite a paucity of experimental data needed to independently validate the method.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Notes
- 1.
“Redundancy” is defined herein as access to multiple NMR J-couplings that report on the same molecular torsion angle, θ. Furthermore, plots of J-coupling magnitude as a function of θ should not be superimposable, but rather should be phase-shifted so as to maximize the ability of these multiple couplings to discrimiate between different conformational models. If the plots overlap, the use of redundant J-couplings will not improve conformational analyses appreciably.
References
Serianni AS, Pierce J, Huang SG, Barker R (1982) Anomerization of furanose sugars: kinetics of ring-opening reactions by 1H and 13C saturation-transfer NMR spectroscopy. J Am Chem Soc 104:4037–4044
Hu X, Zhang W, Carmichael I, Seriani AS (2010) Amide cis-trans isomerization in aqueous solutions of methyl N-formyl-D-glucosaminides and methyl N-acetyl-D-glucosaminides: chemical equilibria and exchange kinetics. J Am Chem Soc 132:4641–4652
Pereira CS, Kony D, Baron R, Müller M, van Gunsteren WF, Hünenberger PH (2006) Conformational and dynamical properties of disaccharides in water: a molecular dynamics study. Biophys J 90:4337–4344
Whitfield ML, Sherlock G, Saldanha AJ, Murray JI, Ball CA, Alexander KE, Matese JC, Perou CM, Hurt MM, Brown PO, Botstein D (2002) Identification of genes periodically expressed in the human cell cycle and their expression in tumors. Mol Biol Cell 13:1977–2000
Kowalewski J, Mäler L, Widmalm G (1998) NMR relaxation studies of oligosaccharides in solution: reorientational dynamics and internal motion. J Mol Liq 78:255–261
Almond A, DeAngelis PL, Blundell CD (2005) Dynamics of hyaluronan oligosaccharides revealed by 15N relaxation. J Am Chem Soc 127:1086–1087
Parr RG, Yang W (1995) Density-functional theory of the electronic structure of molecules. Annu Rev Phys Chem 46:701–728
Taubert S, Konschin HK, Sundholm D (2005) Computational studies of 13C NMR chemical shifts of saccharides. Phys Chem Chem Phys 7:2561–2569
Bose-Basu B, Zajicek J, Bondo G, Zhao S, Kubsch M, Carmichael I, Serianni AS (2000) Deuterium nuclear spin-lattice relaxation times and quadrupolar coupling constants in isotopically labeled saccharides. J Magn Reson 144:207–216
Bryce DL, Grishaev A, Bax A (2005) Measurement of ribose carbon chemical shift tensors for A-form RNA by liquid crystal NMR spectroscopy. J Am Chem Soc 127:7387–7396
Lemieux RU, Kullnig RK, Bernstein HJ, Schneider WG (1958) Configurational effects on the proton magnetic resonance spectra of six-membered ring compounds. J Am Chem Soc 80:6098–6105
Karplus M (1959) Contact electron-spin coupling of nuclear magnetic moments. J Chem Phys 30:11–15
Günther H (1995) NMR spectroscopy: basic principles, concepts and applications in chemistry, 2nd edn. Wiley, Chichester, pp 69–134
Snyder JR, Serianni AS (1986) D-idose: a one- and two-dimensional NMR investigation of solution composition and conformation. J Org Chem 51:2694–2702
Stenutz R, Carmichael I, Widmalm G, Serianni AS (2002) Hydroxymethyl group conformation in saccharides: structural dependencies of 2JHH, 3JHH, and 1JCH spin–spin coupling constants. J Org Chem 67:949–958
Zhao H, Pan Q, Zhang W, Carmichael I, Serianni AS (2007) DFT and NMR studies of 2JCOH, 3JHCOH, and 3JCCOH spin-couplings in saccharides: C-O torsional bias and H-bonding in aqueous solution. J Org Chem 72:7071–7082
Otter A, Bundle DR (1995) Long-range 4J and 5J, including interglycosidic correlations in gradient-enhanced homonuclear COSY experiments of oligosaccharides. J Magn Reson B109:194–201
Barfield M, Dean AM, Fallick CJ, Spear RJ, Sternhell S, Westerman PW (1975) Conformational dependence and mechanisms for long-range hydrogen-hydrogen coupling constants over four bonds. J Am Chem Soc 97:1482–1492
Thibaudeau C, Stenutz R, Hertz B, Klepach T, Zhao S, Wu Q, Carmichael I, Serianni AS (2004) Correlated C-C and C-O bond conformations in saccharide hydroxymethyl groups: parametrization and application of redundant 1H-1H, 13C-1H, and 13C-13C NMR J-couplings. J Am Chem Soc 126:15668–15685
Maiti NC, Zhu Y, Carmichael I, Serianni AS, Anderson VE (2006) 1JCH correlates with alcohol hydrogen bond strength. J Org Chem 71:2878–2880
Jardetzky O (1980) On the nature of molecular conformations inferred from high-resolution NMR. Biochim Biophys Acta 621:227–232
Bukowski R, Morris LC, Woods RJ, Weimar T (2001) Synthesis and conformational analysis of the T-antigen disaccharide β-D-Gal-(1→3)-β-D-GalNAcOMe. Eur J Org Chem 2001:2697–2705
Woods RJ, Pathiaseril A, Wormald MR, Edge CJ, Dwek RA (1998) The high degree of internal flexibility observed for an oligomannose oligosaccharide does not alter the overall topology of the molecule. Eur J Biochem 258:372–386
Dowd MK, Kiely DE, Zhang J (2011) Monte Carlo-based searching as a tool to study carbohydrate structure. Carbohydr Res 346:1140–1148
Woods RJ (1998) Computational carbohydrate chemistry: what theoretical methods can tell us. Glycoconj J 15:209–216
Hsu C-H, Hung S-C, Wu C-Y, Wong C-H (2011) Toward automated oligosaccharide synthesis. Angew Chem Int Ed 50:11872–11923
Zhang W, Oliver AG, Serianni AS (2010) Methyl β-D-galactopyranosyl-(1→4)-β-D-allopyranoside tetrahydrate. Acta Crystallogr C C66:o484–o487
Stenutz R, Shang M, Serianni AS (1999) Methyl β-Lactoside (methyl 4-O-β-D-galactopyranosyl-β-D-glucopyranoside) methanol solvate. Acta Crystallogr C C55:1719–1721
Zhang W, Oliver AG, Vu HM, Duman JG, Serianni AS (2012) Methyl 4-O-β-D-mannopyranosyl β-D-xylopyranoside. Acta Crystallogr C C68:o502–o506
Ham JT, Williams DG (1970) The crystal and molecular structure of methyl β-cellobioside-methanol. Acta Crystallogr C B26:1373–1383
Pan Q, Noll BC, Serianni AS (2005) Methyl 4-O-β-D-galactopyranosyl α-D-glycopyranoside (methyl α-lactoside). Acta Crystallogr C C61:o674–o677
Zhang W, Oliver AG, Serianni AS (2012) Disorder and conformational analysis of methyl β-D-galactopyranosyl-(1→4)-β-D-xylopyranoside. Acta Crystallogr C C68:o7–o11
Hu X, Pan Q, Noll BC, Oliver AG, Serianni AS (2010) Methyl 4-O-β-D-galactopyranosyl α-D-mannopyranoside methanol 0.375-solvate. Acta Crystallogr C C66:o67–o70
Pachler KGR (1971) Extended Hückel theory MO calculations of proton-proton coupling constants – II: the effect of substituents on vicinal couplings in monosubstituted ethanes. Tetrahedron 27:187–199
Galan MC, Venot AP, Glushka J, Imberty A, Boons G-J (2002) Alpha-(2→6)-sialyltransferase-catalyzed sialylations of conformationally constrained oligosaccharides. J Am Chem Soc 124:5964–5973
Hohenberg P, Kohn W (1964) Inhomogeneous electron. Gas Phys Rev 136:B864–B871
Kohn W, Sham LJ (1965) Self-consistent equations including exchange and correlation effects. Phys Rev 140:A1133–A1138
Perdew JP, Wang Y (1986) Accurate and simple density functional for the electronic exchange energy: generalized gradient approximation. Phys Rev B 33:8800–8802
Becke AD (1993) Density-functional thermochemistry. III. The role of exact exchange. J Chem Phys 98:5648–5652
Lee C, Yang W, Parr RG (1988) Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Phys Rev B 37:785–789
Pople JA, McIver JW Jr, Ostlund NS (1967) Finite perturbation theory for nuclear spin coupling constants. Chem Phys Lett 1:465–466
Pople JA, McIver JW Jr, Ostlund NS (1968) Self-consistent perturbation theory. I. Finite perturbation methods. J Chem Phys 49:2960–2964
Pople JA, McIver JW Jr, Ostlund NS (1968) Self-consistent perturbation theory. II. Nuclear spin coupling constants. J Chem Phys 49:2965–2970
Ramsey NF (1953) Electron coupled interactions between nuclear spins in molecules. Phys Rev 91:303–307
Helgaker T, Watson M, Handy NC (2000) Analytical calculation of nuclear magnetic resonance indirect spin–spin coupling constants at the generalized gradient approximation and hybrid levels of density-functional theory. J Chem Phys 113:9402–9409
Miertus S, Scrocco E, Tomasi J (1981) Electrostatic interaction of a solute with a continuum. A direct utilization of ab inito molecular potentials for the provision of solvent effects. Chem Phys 55:117–129
Cancés E, Mennucci B (1998) New applications of integral equations methods for solvation continuum models: ionic solutions and liquid crystals. J Math Chem 23:309–326
Cancés E, Mennucci B, Tomasi J (1997) A new integral equation formalism for the polarizable continuum model: theoretical background and applications to isotropic and anisotropic dielectrics. J Chem Phys 107:3032–3041
Mennucci B, Cancés E, Tomasi J (1997) Evaluation of solvent effects in isotropic and anisotropic dielectrics and in ionic solutions with a unified integral equation method: theoretical bases, computational implementation, and numerical applications. J Phys Chem B 101:10506–10517
Tomasi J, Mennucci B, Cammi R (2005) Quantum mechanical continuum solvation models. Chem Rev 105:2999–3093
Bose B, Zhao S, Stenutz R, Cloran F, Bondo PB, Bondo G, Hertz B, Carmichael I, Serianni AS (1998) Three-bond C-O-C-C spin-coupling constants in carbohydrates: development of a Karplus relationship. J Am Chem Soc 120:11158–11173
Haasnoot CAG, de Leeuw FAAM, Altona C (1980) The relationship between proton-proton NMR coupling constants and substituent electronegativities—I: an empirical generalization of the Karplus equation. Tetrahedron 36:2783–2792
Altona C, Ippel JH, Hoekzema AJAW, Erkelens C, Groesbeek M, Donders LA (1989) Relationship between proton-proton NMR coupling constants and substituent electronegativities. V. Empirical substituent constants deduced from ethanes and propanes. Magn Reson Chem 27:564–576
Altona C, Francke R, de Haan R, Ippel JH, Daalmans GJ, Hoekzema AJAW, van Wijk J (1994) Empirical group electronegativities for vicinal NMR proton-proton couplings along a C-C bond: solvent effects and reparameterization of the Haasnoot equation. Magn Reson Chem 32:670–678
Carmichael I, Chipman DM, Podlasek CA, Serianni AS (1993) Torsional effects on the one-bond 13C-13C spin coupling constant in ethylene glycol: insights into the behavior of 1JCC in carbohydrates. J Am Chem Soc 115:10863–10870
Church T, Carmichael I, Serianni AS (1996) Two-bond 13C-13C spin-coupling constants in carbohydrates: effect of structure on coupling magnitude and sign. Carbohydr Res 280:177–186
Serianni AS, Bondo PB, Zajicek J (1996) Verification of the projection resultant method for two-bond 13C-13C coupling sign determinations in carbohydrates. J Magn Reson Ser B 112:69–74
Klepach T, Serianni AS (unpublished results)
Cloran F, Carmichael I, Serianni AS (2000) 2JCOC spin-spin coupling constants across glycosidic linkages exhibit a valence bond-angle dependence. J Am Chem Soc 122:396–397
Cloran F, Carmichael I, Serianni AS (1999) Density functional calculations on disaccharide mimics: studies of molecular geometries and trans-O-glycosidic 3JCOCH and 3JCOCC spin-couplings. J Am Chem Soc 121:9843–9851
Bose-Basu B, Klepach T, Bondo G, Bondo PB, Zhang W, Carmichael I, Serianni AS (2007) 13C–13C NMR spin-spin coupling constants in saccharides: structural correlations involving all carbons in aldohexopyranosyl rings. J Org Chem 72:7511–7522
Müller N, Pritchard DE (1959) C13 splittings in proton magnetic resonance spectra. I. Hydrocarbons. J Chem Phys 31:768–771
Serianni AS, Wu J, Carmichael I (1995) One-Bond 13C-1H spin-coupling constants in aldofuranosyl rings: effect of conformation on coupling magnitude. J Am Chem Soc 117:8645–8650
Bock K, Pedersen C (1977) Two- and three-bond 13C-1H couplings in some carbohydrates. Acta Chem Scand B 31:354–358
Klepach TE, Carmichael I, Serianni AS (2005) Geminal 2JCCH spin-spin coupling constants as probes of the ϕ glycosidic torsion angle in oligosaccharides. J Am Chem Soc 127:9781–9793
Podlasek CA, Wu J, Stripe WA, Bondo PB, Serianni AS (1995) [13C]-Enriched methyl aldopyranosides: structural interpretations of 13C–1H spin-coupling constants and 1H chemical shifts. J Am Chem Soc 117:8635–8644
ChemBio3D. www.cambridgesoft.com/Ensemble_for_Biology/ChemBio3D/Default.aspx
Spartan. www.wavefun.com/products/spartan.html
Dennington R, Keith T, Millam J (2009) GaussView, Version 5. Semichem Inc., Shawnee Mission, KS
GAMESS. www.msg.ameslab.gov/gamess/
Jaguar. www.schrodinger.com/products/14/7/
Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Scalmani G, Barone V, Mennucci B, Petersson GA, Nakatsuji H, Caricato M, Li X, Hratchian HP, Izmaylov AF, Bloino J, Zheng G, Sonnenberg JL, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Vreven T, Montgomery JA Jr, Peralta JE, Ogliaro F, Bearpark M, Heyd JJ, Brothers E, Kudin KN, Staroverov VN, Kobayashi R, Normand J, Raghavachari K, Rendell A, Burant JC, Iyengar SS, Tomasi J, Cossi M, Rega N, Millam JM, Klene M, Knox JE, Cross JB, Bakken V, Adamo C, Jaramillo J, Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski JW, Martin RL, Morokuma K, Zakrzewski VG, Voth GA, Salvador P, Dannenberg JJ, Dapprich S, Daniels AD, Farkas Ö, Foresman JB, Ortiz JV, Cioslowski J, Fox DJ (2009) Gaussian 09, Revision A.1. Gaussian Inc., Wallingford, CT
Hehre WJ, Ditchfield R, Pople JA (1972) Self-consistent molecular orbital methods. XII. Further extensions of Gaussian-type basis sets for use in molecular orbital studies of organic molecules. J Chem Phys 56:2257–2261
York DM, Karplus M (1999) A smooth solvation potential based on the conductor-like screening model. J Phys Chem A 103:11060–11079
Sychrovsky V, Gräfenstein J, Cremer D (2000) Nuclear magnetic resonance spin-spin coupling constants from coupled perturbed density functional theory. J Chem Phys 113:3530–3547
Carmichael I (1993) Ab initio quadratic configuration interaction calculation of indirect NMR spin-spin coupling constants. J Phys Chem 97:1789–1792
King-Morris MJ, Serianni AS (1987) 13C NMR studies of [1-13C] aldoses: empirical rules correlating pyranose ring configuration and conformation with 13C chemical shifts and 13C-13C spin couplings. J Am Chem Soc 109:3501–3508
Wu J, Bondo PB, Vuorinen T, Serianni A (1992) 13C–13C spin coupling constants in aldoses enriched with 13C at the terminal hydroxymethyl carbon: effect of coupling pathway structure on JCC in carbohydrates. J Am Chem Soc 114:3499–3505
Zhao H, Carmichael I, Serianni AS (2008) Oligosaccharide trans-glycoside 3JCOCC Karplus curves are not equivalent: effect of internal electronegative substituents. J Org Chem 73:3255–3257
Serianni AS, Podlasek CA (1994) 13C-1H spin-coupling constants in carbohydrates: magnitude and sign determinations via 2D NMR methods. Carbohydr Res 259:277–282
Muslim A-M, McNamara JP, Abdel-Aal H, Hillier IH, Bryce RA (2006) QM/MM simulations of carbohydrates. In: NMR spectroscopy and computer modeling of carbohydrates. ACS Symposium Series 2006, vol 930. American Chemical Society. pp 186–202
Thureau P, Mollica G, Ziarelli F, Viel S (2013) Selective measurements of long-range homonuclear J-couplings in solid-state NMR. J Magn Reson 231:90–94
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2015 Springer Science+Business Media New York
About this protocol
Cite this protocol
Klepach, T. et al. (2015). Informing Saccharide Structural NMR Studies with Density Functional Theory Calculations. In: Lütteke, T., Frank, M. (eds) Glycoinformatics. Methods in Molecular Biology, vol 1273. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2343-4_20
Download citation
DOI: https://doi.org/10.1007/978-1-4939-2343-4_20
Published:
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-2342-7
Online ISBN: 978-1-4939-2343-4
eBook Packages: Springer Protocols